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Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases...
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Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases in Patients with Diabetes Mellitus

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (26 February 2024) | Viewed by 6455

Special Issue Editor

Dr. Nikolaos Kadoglou

E-Mail Website
Guest Editor
Medical School, University of Cyprus, 2029 Nicosia, Cyprus
Interests: cardiovascular disease prevention; atherosclerotic plaque vulnerability; heart failure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes mellitus (DM) has already evolved into an epidemic in developing countries, and especially in the western world. It is well-known that diabetic patients have a 2- to 4-fold higher risk for cardiovascular diseases (CVDs). Moreover, the presence of DM remarkably increases the incidence of cardiovascular events in patients with established CVDs despite the administration of optimum pharmaceutical therapy. The re-vascularization procedures in coronary and peripheral arteries are characterized by a higher incidence of complications in patients with DM than their non-diabetic counterparts. Therefore, there is still an increasing need to develop and apply more effective medications for primary and secondary prevention of CVDs (ischemic and non-ischemic) in the DM population. 

The aim of the present Special Issue is to attract more than 10 high-quality papers that focus on drugs with potentiality to contribute to CVD prevention and treatment in diabetic patients. Those drug candidates may be substances that target several aspects of pathophysiological mechanisms of CVDs or may comprise therapeutic regimes of other, non-cardiovascular diseases, with potential expansion of their indications to CVDs. Among all, established and novel, especially gene-oriented, lipid-lowering agents remain the cornerstone of prevention and treatment of ischemic CVDs. Medicinal chemistry has introduced technological and conceptual innovations with wide potential application in CVDs. In this Special Issue, we also expect manuscripts providing evidence or summarizing the expanding cardiovascular benefits of current anti-diabetic medications, such as sodium–glucose co-transporter 2 inhibitors, or of candidate drugs. The anti-inflammatory agents and immunomodulators used in auto-immune diseases have opened a new era in the pharmaceutical treatment of patients with CVDs. In addition to this, other drugs targeting the main pathophysiological mechanisms of myocardial or vascular remodeling, such as the inhibition of myocardial fibrosis or vascular wall inflammatory infiltration, respectively, are also quite promising. Finally, herbal medicine remains a very promising source of drug candidates and requires further investigation. These taken together, there is an increasing number of drugs that could serve effectively in the primary and secondary prevention of CVDs in DM in order to improve the survival and the quality of life of diabetic patients.

Dr. Nikolaos Kadoglou
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • diabetes mellitus
  • lipid lowering
  • anti-diabetic drugs
  • hypercholesterolemia
  • hypertriglyceridemia
  • PCSK9
  • SGLT-2
  • immunomodulators
  • gene therapy
  • anti-inflammatory drugs
  • regenerative medicine
  • herbal medicine

Published Papers (4 papers)

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Research

18 pages, 4715 KiB  
Article
Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus
by Shatha M. Alobaid, Rahaf M. Alshahrani, Asma S. Alonazi, Nawal M. Alrasheed, Maha A. Alamin, Tahani K. Alshammari, Anfal F. Bin Dayel, Doaa M. Elnagar, Rana R. Alotaibi, Lama A. Almuthnabi, Dalia H. Almasud, Shahad E. Al-Ammar, Shahad O. Almadhi, Reema A. Almalke, Nouf T. Aldamri, Hanan K. Alghibiwi, Dalal A. Alkhelb and Nouf M. Alrasheed
Pharmaceuticals 2024, 17(3), 374; https://doi.org/10.3390/ph17030374 - 15 Mar 2024
Viewed by 997
Abstract
One of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were [...] Read more.
One of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were examined. Twenty-four Wistar albino rats were distributed in four different groups, and a high-fat diet and streptozotocin were used to induce type 2 in two groups. Rats in the untreated control groups were administered 0.9% NaCl solution over a 6-week period, and those in the treatment groups were administered 0.9% NaCl for 3 weeks, followed by subcutaneous injection of liraglutide (150 μg/kg) for an additional 3 weeks. In the liraglutide-treated diabetic group, the heart-to-body weight ratio was significantly reduced, levels of cardiac biomarkers, troponin I and creatine-kinase-MB, were improved; activities of antioxidant enzymes, glutathione peroxidase and superoxide dismutase, were increased; and levels of malondialdehyde were decreased. Western blotting and immunohistochemical studies revealed increased levels of ILK, P-PI3K, P-AKT, and BCL2, as well as those of caspase 3, BAX, and P-PTEN, indicating mitigation of cardiomyocyte apoptosis. Our results show that liraglutide, by targeting GLP1Rs, enhances the expression of proteins in the ILK/PI3K/AKT/PTEN pathway and thereby exerts its cardioprotective effects in rats with DCM. Full article
(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases in Patients with Diabetes Mellitus)
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12 pages, 3153 KiB  
Article
The Complementary Effects of Dabigatran Etexilate and Exercise Training on the Development and Stability of the Atherosclerotic Lesions in Diabetic ApoE Knockout Mice
by Nikolaos PE Kadoglou, Marianna Stasinopoulou, Evangelia Gkougkoudi, Eirini Christodoulou, Nikolaos Kostomitsopoulos and Georgia Valsami
Pharmaceuticals 2023, 16(10), 1396; https://doi.org/10.3390/ph16101396 - 02 Oct 2023
Viewed by 791
Abstract
Aim: To determine the complementary effects of dabigatran etexilate (DE), exercise training (ET), and combination (DE + ET) on the development and stability of the atherosclerotic lesions in diabetic apoE knockout (apoE−/−) mice. Methods: In 48 male apoE−/− diabetic mice, [...] Read more.
Aim: To determine the complementary effects of dabigatran etexilate (DE), exercise training (ET), and combination (DE + ET) on the development and stability of the atherosclerotic lesions in diabetic apoE knockout (apoE−/−) mice. Methods: In 48 male apoE−/− diabetic mice, streptozotocin (STZ) was induced for 5 consecutive days. Mice received a high-fat diet (HFD) for 8 weeks and then were randomized into four groups (1. Control/CG, 2. DEG: HFD with DE, 3. ETG: ET on treadmill, 4. DE + ETG: combination DE and ET treatment). At the end of the eighth week, all mice were euthanatized and morphometry of the aortic lesions at the level of aortic valve was obtained. Collagen, elastin, MCP-1, TNF-a, matrix metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations within plaques at the aortic valve were determined. Results: All active groups had significantly smaller aorta stenosis (DEG:7.9 ± 2.2%, ETG:17.3 ± 5.3%, DE + ETG:7.1 ± 2.7%) compared to CG (23.3 ± 5.5% p < 0.05), reduced the relative intra-plaque content of MCP-1, macrophages, MMP-3, and MMP-9, and considerably increased collagen, elastin, and TIMP-1 (p < 0.05). Group 4 showed the most pronounced results (p < 0.05). Both DEG and DE + ETG significantly reduced MMP-2 and TNF-a concentrations compared to ETG and CG (p < 0.010). Conclusion: DE and ET treatment of diabetic apoE−/− mice resulted in complementary amelioration of atherosclerotic lesions development and stability, mediated by the anti-inflammatory modulation of both DE and ET. Full article
(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases in Patients with Diabetes Mellitus)
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15 pages, 3338 KiB  
Article
Does Therapy with Glucagon-like Peptide 1 Receptor Agonists Have an Effect on Biochemical Markers of Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD)? Pleiotropic Metabolic Effect of Novel Antidiabetic Drugs in Patients with Diabetes—Interventional Study
by Marcin Hachuła, Michał Kosowski, Marcin Basiak and Bogusław Okopień
Pharmaceuticals 2023, 16(9), 1190; https://doi.org/10.3390/ph16091190 - 22 Aug 2023
Cited by 1 | Viewed by 1443
Abstract
Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) is associated with the excessive collection of lipids in hepatocytes. Over 75% of diabetes patients typically have MASLD, and, at the same time, the presence of MASLD increases the risk of diabetes by more than two times. [...] Read more.
Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) is associated with the excessive collection of lipids in hepatocytes. Over 75% of diabetes patients typically have MASLD, and, at the same time, the presence of MASLD increases the risk of diabetes by more than two times. Type 2 diabetes and MASLD are independent cardiovascular disease (CVD) risk factors. New diabetes treatment should also take into account pleiotropic effects that reduce cardiovascular risk. The aim of our study is to investigate whether analogs of GLP1 receptors have a pleiotropic metabolic effect and global impact to decrease cardiovascular risk, and also reduce the risk of hepatic fibrosis in patients with MASLD. This study involved 41 patients with diabetes and dyslipidemia who also had atherosclerotic plaque and hepatic steatosis verified by ultrasonography and who were eligible to begin one of the GLP1 receptor agonists treatments. We observed a statistically significant decrease in: BMI (p < 0.001) waist and hip circumference (p < 0.001), glycated hemoglobin (p < 0.001) and creatinine (p < 0.05). Additionally, we obtained a decrease in FIB-4 (p < 0.001) and in the De Ritis (AST/ALT aminotransferase ratio) (p < 0.05). The positive correlation between the FIB-4 value and BMI, WHR, waist circumference and the De Ritis index was observed. In conclusion, semaglutide and dulaglutide had a beneficial effect on metabolic and cardiovascular risk factors in patients with type 2 diabetes. These medications had a positive effect on MASLD biochemical markers. Full article
(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases in Patients with Diabetes Mellitus)
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17 pages, 1682 KiB  
Article
Effects of Statin Dose, Class, and Use Intensity on All-Cause Mortality in Patients with Type 2 Diabetes Mellitus
by Jung-Min Yu, Wan-Ming Chen, Mingchih Chen, Ben-Chang Shia and Szu-Yuan Wu
Pharmaceuticals 2023, 16(4), 507; https://doi.org/10.3390/ph16040507 - 29 Mar 2023
Cited by 3 | Viewed by 2720
Abstract
Purpose: to examine the impact of statins on reducing all-cause mortality among individuals diagnosed with type 2 diabetes. This investigation explored the potential correlations between dosage, drug classification, and usage intensity with the observed outcomes. Methods: The research sample consisted of individuals aged [...] Read more.
Purpose: to examine the impact of statins on reducing all-cause mortality among individuals diagnosed with type 2 diabetes. This investigation explored the potential correlations between dosage, drug classification, and usage intensity with the observed outcomes. Methods: The research sample consisted of individuals aged 40 years or older diagnosed with type 2 diabetes. Statin usage was determined as a frequent usage over a minimum of one month subsequent to type 2 diabetes diagnosis, where the average statin dose was ≥28 cumulative defined daily doses per year (cDDD-year). The analysis employed an inverse probability of treatment-weighted Cox hazard model, utilizing statin usage status as a time-varying variable, to evaluate the impact of statin use on all-cause mortality. Results: The incidence of mortality was comparatively lower among the cohort of statin users (n = 50,804 (12.03%)), in contrast to nonusers (n = 118,765 (27.79%)). After adjustments, the hazard ratio (aHR; 95% confidence interval (CI)) for all-cause mortality was estimated to be 0.32 (0.31–0.33). Compared with nonusers, pitavastatin, rosuvastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and lovastatin users demonstrated significant reductions in all-cause mortality (aHRs (95% CIs) = 0.06 (0.04–0.09), 0.28 (0.27–0.29), 0.29 (0.28–0.31), 0.31 (0.30–0.32), 0.31 (0.30–0.32), 0.36 (0.35–0.38), and 0.48 (0.47–0.50), respectively). In Q1, Q2, Q3, and Q4 of cDDD-year, our multivariate analysis demonstrated significant reductions in all-cause mortality (aHRs (95% CIs) = 0.51 (0.5–0.52), 0.36 (0.35–0.37), 0.24 (0.23–0.25), and 0.13 (0.13–0.14), respectively; p for trend <0.0001). Because it had the lowest aHR (0.32), 0.86 DDD of statin was considered optimal. Conclusions: In patients diagnosed with type 2 diabetes, consistent utilization of statins (≥28 cumulative defined daily doses per year) was shown to have a beneficial effect on all-cause mortality. Moreover, the risk of all-cause mortality decreased as the cumulative defined daily dose per year of statin increased. Full article
(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases in Patients with Diabetes Mellitus)
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